Impact of Histone H1 on the Progression of Allergic Rhinitis and Its Suppression by Neutralizing Antibody in Mice

Nuclear antigens are known to trigger off innate and adaptive immune responses. Recent studies have found that the complex of nucleic acids and core histones that are derived from damaged cells may regulate allergic responses. However, no fundamental study has been performed concerning the role of linker histone H1 in mast cell-mediated type I hyperreactivity. In this study, we explored the impact of histone H1 on mast cell-mediated allergic responses both in vitro and in vivo. In the course of a bona-fide experimental allergen sensitization model upon co-injection with alum adjuvant, ovalbumin (OVA), but not PBS, induced elevated levels of circulating histone H1. Intranasal challenge with histone H1 to OVA/alum- (but not PBS/alum)-sensitized mice induced significantly severer symptoms of allergic rhinitis than those in mice sensitized and challenged with OVA. A monoclonal antibody against histone H1 not only suppressed mast cell degranulation, but also ameliorated OVA-induced nasal hyperreactivity and IgE-mediated passive cutaneous anaphylaxis. Our present data suggest that nuclear histone H1 represents an alarmin-like endogenous mediator acting on mast cells, and that its blockage has a therapeutic potential for mast cell-mediated type I hyperreactivity.     

Alterations and Mechanism of Gut Microbiota in Graves’ Disease and Hashimoto’s Thyroiditis

To explore the role of gut microbiota in Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Seventy fecal samples were collected, including 27 patients with GD, 27 with HT, and 16 samples from healthy volunteers. Chemiluminescence was used to detect thyroid function and autoantibodies (FT3, FT4, TSH, TRAb, TGAb, and TPOAb); thyroid ultrasound and 16S sequencing were used to analyze the bacteria in fecal samples; KEGG (Kyoto Encyclopedia of Genes and Genomes) and COG (Clusters of Orthologous Groups) were used to analyze the functional prediction and pathogenesis. The overall structure of gut microbiota in the GD and HT groups was significantly different from the healthy control group. Proteobacteria and Actinobacteria contents were the highest in the HT group. Compared to the control group, the GD and HT groups had a higher abundance of Erysipelotrichia, Cyanobacteria, and Ruminococcus_2 and lower levels of Bacillaceae and Megamonas. Further analysis of KEGG found that the “ABC transporter” metabolic pathway was highly correlated with the occurrence of GD and HT. COG analysis showed that the GD and HT groups were enriched in carbohydrate transport and metabolism compared to the healthy control group but not in amino acid transport and metabolism. Our data suggested that Bacillus, Blautia, and Ornithinimicrobium could be used as potential markers to distinguish GD and HT from the healthy population and that “ABC transporter” metabolic pathway may be involved in the pathogenesis of GD and HT.     

Regulation of alternative splicing of Bcl-x by IL-6, GM-CSF and TPA

The splicing of many alternative exons in the precursor messenger RNA (pre-mRNA) is regulated by extracellular factors but the underlying molecular bases remain unclear. Here we report the differential regulation of Bcl-x pre-mRNA splicing by extracellular factors and their distinct requirements for pre-mRNA elements. In K562 leukemia cells, treatment with interleukin-6 (IL-6) or granulocyte-macrophage colony stimulating factor (GM-CSF) reduced the proportion of the Bcl-xL variant mRNA while treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) had no effect. In U251 glioma cells, however, TPA efficiently increased the Bcl-xL level. These regulations were also seen for a transfected splicing reporter mini-gene. Further analyses of deletion mutants indicate that nucleotides 1-176 of the downstream intron are required for the IL-6 effect, whereas additional nucleotides 177-284 are essential for the GM-CSF effect. As for the TPA effect, only nucleotides 1-76 are required in the downstream intron. Thus, IL-6, GM-CSF and TPA differentially regulate Bcl-x splicing and require specific intronic pre-mRNA sequences for their respective effects.     

Inhibition of human NTPDase 2 by modification of an intramembrane cysteine by p-chloromercuriphenylsulfonate and oxidative cross-linking of the transmembrane domains

Human NTPDase 2 is a cell surface integral membrane glycoprotein that is anchored to the membranes by two transmembrane domains while the bulk of the protein containing the active site faces the extracellular milieu. It contains 10 conserved cysteine residues in the extracellular domain that are involved in disulfide bond formation and one free cysteine residue, C26, which is located in the N-terminal transmembrane domain. The human NTPDase 2 activity is inactivated by membrane perturbation that disrupts interaction of the transmembrane domains and is inhibited by p-chloromercuriphenylsulfonate (pCMPS), a sulfhydryl reagent. In this report, we show that C26 is the target of pCMPS modification, since a mutant in which C26 was replaced with a serine was no longer inhibited by pCMPS. Mutants in which cysteine residues are placed in the C-terminal transmembrane domain near the extracellular surface were still modified by pCMPS, but the degree of inhibition of their ATPase activity was lower than that of the wild-type enzyme. Thus, loss of the ATPase activity of human NTPDase 2 in the presence of pCMPS probably results from the disturbance of both transmembrane domain interaction and its active site. Inhibition of human NTPDase 2 activity by pCMPS and membrane perturbation is attenuated when the enzyme is cross-linked by glutaraldehyde. On the other hand, NTPDase 2 dimers formed from oxidative cross-linking of the wild-type enzyme and mutants containing a single cysteine residue in the C-terminal transmembrane domain displayed reduced ATPase activity. A similar reduction in activity was also obtained upon intramolecular disulfide formation in mutants that contain a cysteine residue in each of the two transmembrane domains. These results indicate that the mobility of the transmembrane helices is necessary for maximal catalysis.     

P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics

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Microbial boundstone dominated carbonate slope (Upper Carboniferous,N Spain): Microfacies,lithofacies distribution and stratal geometry

Summary The Carboniferous, particularly during the Serpukhovian and Bashkirian time, was a period of scarce shallow-water calcimicrobial-microbialite reef growth. Organic frameworks developed on high-rising platforms are, however, recorded in the Precaspian Basin subsurface, Kazakhstan, Russia, Japan and Spain and represent uncommon occurrences within the general trend of low accumulation rates and scarcity of shallow-water reefs. Sierra del Cuera (Cantabrian Mountains, N Spain) is a well-exposed high-rising carbonate platform of Late Carboniferous (Bashkirian-Moscovian) age with a microbial boundstone-dominated slope dipping from 20° up to 45°. Kilometer-scale continuous exposures allow the detailed documentation of slope geometry and lithofacies spatial distribution. This study aims to develop a depositional model of steep-margined Late Paleozoic platforms built by microbial carbonates and to contribute to the understanding of the controlling factors on lithofacies characteristics, stacking patterns, accumulation rates and evolution of the depositional architecture of systems, which differ from light-dependent coralgal platform margins. From the platform break to depths of nearly 300 m, the slope is dominated by massive cement-rich boundstone, which accumulated through the biologically induced precipitation of micrite. Boundstone facies (type A) with peloidal carbonate mud, fenestellid and fistuliporid bryozoans, sponge-like molds and primary cavities filled by radiaxial fibrous cement occurs all over the slope but dominates the deeper settings. Type B boundstone consists of globose centimeter-scale laminated accretionary structures, which commonly host botryoidal cement in growth cavities. The laminae nucleate around fenestellid bryozoans, sponges, Renalcis and Girvanella-like filaments. Type B boundstone typically occurs at depths between 20–150 m to locally more than 300 m and forms the bulk of the Bashkirian prograding slope. The uppermost slope boundstone (type C; between 0 and 20–100 m depth) includes peloidal micrite, radiaxial fibrous cement, bryozoans, sponge molds, Donezella, Renalcis, Girvanella, Ortonella, calcareous algae and calcitornellid foraminifers. From depths of 80–200 m to 450 m, 1–30 m thick lenses of crinoidal packstone, spiculitic wackestone, and bryozoan biocementstone with red-stained micrite matrix are episodically intercalated with boundstone and breccias. These layers increase in number from the uppermost Bashkirian to the Moscovian in parallel with the change from a rapidly prograding to an aggrading architecture. The red-stained strata share comparable features with Lower Carboniferous deeper-water mud-mound facies and were deposited during relative rises of sea level and pauses in boundstone production. Rapid relative sea-level rises might have been associated with changes in oceanographic conditions not favourable for thecalcimicrobial boundstone growth, such as upwelling of colder, nutrient-rich waters lifting the thermocline to depths of 80–200 m. Downslope of 150–300 m, boundstones interfinger with layers of matrix-free breccias, lenses of matrix-rich breccias, platform- and slope-derived grainstone and crinoidal packstone. Clast-supported breccias bound by radiaxial cement are produced by rock falls and avalanches coeval to boundstone growth. Matrix-rich breccias are debris flow deposits triggered by the accumulation of red-stained layers. Debris flows develop following the relative sea-level rises, which favour the deposition of micrite-rich lithofacies on the slope rather than being related to relative sea-level falls and subaerial exposures. The steep slope angles are the result of in situ growth and rapid stabilization by marine cement in the uppermost part, passing into a detrital talus, which rests at the angle of repose of noncohesive material. In the Moscovian, the aggradational architecture and steeper clinoforms are the result of increased accommodation space due to tectonic subsidence and due to a reduction of slope accumulation rates (from 240±45−605±35 m/My to 130±5 m/My). The increasing number of red-stained layers and the decrease of boundstone productivity are attributed to environmental changes in the adjacent basin, in particular during relative rises of sea level and to possible cooling due to icehouse conditions. The geometry of the depositional system appears to be controlled by boundstone growth rates. During the Bashkirian, the boundstone growth potential is at least 10 times greater than average values for ancient carbonate systems. The slope progradation rates (nearly 400–1000 m/My) are similar to the highest values deduced for the Holocene Bahamian prograding platform margin. The fundamental differences with modern systems are that progradation of the microbial-boundstone dominated steep slope is primarily controlled by boundstone growth rates rather than by highstand shedding from the platform top and that boundstone growth is largely independent from light and controlled by the physicochemical characteristics of seawater.     

Drought enhances maize chilling tolerance. II. Photosynthetic traits and protective mechanisms against oxidative stress

In the present research we studied the photosynthetic traits and protective mechanisms against oxidative stress in two maize ( Zea mays L.) genotypes differing in chilling sensitivity (Z7, tolerant and Penjalinan, sensitive) subjected to 5°C for 5 days, with or without pretreatment by drought. The drought pretreatment decreased the symptoms of chilling injury in Penjalinan plants estimated as necrotic leaf area and maximum quantum yield of photosystem II. Furthermore, drought pretreatment diminished the level of lipid peroxidation caused by chilling in Penjalinan plants. After one day of recovery from chilling the Z7 and drought-pretreated Penjalinan plants showed higher net photosynthesis rates than the non-drought-pretreated Penjalinan plants, thereby decreasing the probability of generating reactive oxygen species. The greater net photosynthesis was correlated with the greater NADP-malate dehydrogenase activity. No differences in either the de-epoxidation state of the xanthophyll cycle or the antioxidant enzyme activities were found among the chilled groups of plants. However, a drastic decrease in ascorbate content was observed in chilled Penjalinan plants without drought pretreatment. As we found an increase of H₂O₂ content after drought pretreatment, we suggest its involvement as a signal in the drought-enhanced chilling tolerance of maize.     

Changes in native and introduced host–parasite networks

Biological Invasions - Introduced species can alter the dynamics and structure of a native community. Network analysis provides a tool to study host–parasite interactions that can help to...